Triple Low-Dose Antihypertensive Pill Reduced Recurrent Stroke After intracerebral hemorrhage
KEY TAKEAWAYS
- A fixed-dose triple antihypertensive pill reduced recurrent stroke risk by ~39% vs placebo.
- Improvements in blood pressure control were sustained, with a ~9 mm Hg lower systolic BP during follow-up.
- Serious adverse events were similar between groups, though treatment discontinuation was higher with the combination pill.
A fixed-dose combination of 3 low-dose antihypertensive agents significantly reduced the risk of recurrent stroke in participants with prior intracerebral hemorrhage (ICH), according to findings from a multinational randomized trial published in The New England Journal of Medicine. The therapy, delivered as a single daily “triple pill” in addition to standard care, also improved long-term blood pressure control and lowered major cardiovascular events, supporting a simplified approach to secondary stroke prevention.
The double-blind, placebo-controlled TRIDENT trial (NCT02699645) enrolled 1670 adults with a history of spontaneous ICH and baseline systolic blood pressure of 130 to 160 mm Hg. After a short run-in phase with the combination therapy (telmisartan, amlodipine, and indapamide at low doses), participants were randomized to continue the triple pill (n=833) or switch to placebo (n=837), with both groups receiving standard antihypertensive care. The primary outcome was time to first recurrent stroke, with secondary end points including blood pressure control, major cardiovascular events, and safety outcomes.
Key Findings
- Recurrent stroke occurred in 4.6% of participants receiving the triple pill vs 7.4% with placebo (hazard ratio [HR], 0.61; 95% CI, 0.41 to 0.92).
- Mean systolic blood pressure during follow-up was 127 mm Hg with the triple pill vs 138 mm Hg with placebo.
- Major cardiovascular events were less frequent with the triple pill (6.6% vs 9.8%; HR, 0.67; 95% CI, 0.47 to 0.94).
- Blood pressure control (<130 mm Hg) at 6 months was achieved in 49.9% vs 26.4% of patients, respectively (odds ratio, 3.15; 95% CI, 2.53 to 3.92).
Serious adverse events occurred at similar rates between groups, although discontinuation due to adverse events was more frequent in the triple-pill group.
Source
The Trident Research Group. Three low-dose antihypertensive agents in a single pill after intracerebral hemorrhage. N Engl J Med. 2026;394(16):1571-1582. doi:10.1056/NEJMoa2515043